Ocular involvement is common in systemic autoimmune disorders. Among the lesions seen are uveitis with the spondyloarthropathies, scleritis with rheumatoid arthritis and vasculitis, and Sjogren's syndrome with rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. We have investigated the ocular and lacrimal gland lesions which spontaneously develop in genetically predetermined autoimmune mice, including MRL/Mp- lpr/lpr (MRL/lpr), MRl/Mp-+/+(MRL/+) and NZBXNZW F1 hybrid (NZB/W) mice. These three mouse strains develop lacrimal gland inflammatory infiltrates which are a model for the human disorder Sjogren's syndrome. We have shown that each mouse differs with respect to time course and immunohistochemical profile of the infiltrating mononuclear inflammatory cells. In addition, MRL/lpr mice develop choroiditis and scleritis, which are not seen either MRL/+ or NZB/W strains. Further investigations of these animal models have now been designed to address the mechanisms by which lacrimal gland damage occurs in all three of these autoimmune mice. These studies will involve: 1) therapeutic intervention in vivo with monoclonal antibodies to cell surface markers to ameliorate the disease and thus define the roles played by specific cell types in the disease process; 2) in vivo treatment with cyclosporine, a selective T cell inhibitor, to investigate the interrelationships of the different arms of the autoimmune response in these mice; and 3) in evaluation of the immunopathogenic mechanisms responsible for lacrimal gland inflammation. In a second set of experiments, we will study the immunopathogenesis of the scleritis and choroiditis seen in MRL/lpr mice. These experiments will include therapeutic intervention with monoclonal antibodies to lymphocyte cell surface markers and treatment with cyclosporine to suppress the autoimmune ocular disease in this strain and thus investigate the roles played by different arms of the immune response in these ocular diseases.